Abstract
An indirect competitive binding mechanism can be exploited to allow a combination of cationic fluorophores and water-soluble synthetic receptors to selectively recognize and discriminate peptide strands containing a single isomeric residue in the backbone. Peptide isomerization occurs in long-lived proteins and has been linked with diseases such as Alzheimer's, cataracts and cancer, so isomers are valuable yet underexplored targets for selective recognition. Planar cationic fluorophores can selectively bind hydrophobic, Trp-containing peptide strands in solution, and when paired with receptors that provide a competitive host for the fluorophore, can form a differential sensing array that enables selective discrimination of peptide isomers. Residue variations such as D- and L-Asp, D- and L-isoAsp, D-Ser and D-Glu can all be recognized, simply by their effects on the folded structure of the flexible peptide. Molecular dynamics simulations were applied to determine the most favorable conformation of the peptide : fluorophore conjugate, indicating that favorable π-stacking with internal tryptophan residues in a folded binding pocket enables micromolar binding affinity.